While it is generally accepted that left ventricular relaxation is an active, energy requiring process, controversy exists as to whether the left ventricle is capable of developing a "suction" pressure that would enable filling to take place even with no or low source pressure to drive filling. Previous studies have demonstrated negative left ventricular pressures in non- physiologic animal models (i.e., with mitral valve occlusion) and in humans with mitral stenosis. It has been speculated that negative LV pressure or "suction" might be present and beneficial in normal humans with exercise. In the present study, we used isoproterenol infusion to simulate conditions of exercise (during catheterization study of coronary reserve in patients with chest pain and normal coronary arteries), and found that negative LV pressure could in fact be demonstrated in almost all cases. The results shed light on the mechanisms by which the normal human heart is able to dramatically increase cardiac output during exercise at high heart rates, when left ventricular filling must be extremely rapid.